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Pathway Description
Lactose Synthesis
Homo sapiens
Metabolic Pathway
Created: 2013-08-01
Last Updated: 2023-10-12
Lactose synthesis occurs only in the mammary glands, producing lactose (4-O-B-D-galactosylpyranosyl-a-D-glucopyranoside), the major sugar in milk. Lactose is created by joining two monosaccarides with a B1,4 glycosidic bond. Glucose is first converted to UDP-galactose via the enzyme galactose-1-phosphate uridylyltransferase. UDP-galactose is then transported into the Golgi by the UDP galactose translocator, an antiporter which uses facilitated transport to move UDP galactose into the Golgi and exports UMP. Once inside the Golgi, the UDP galactose and glucose (which moves into the golgi via the GLUT-1 transporter) become substrates for the lactose synthase enzyme complex, comprised of the enzymatic subunit, galactosyltransferase with its regulatory subunit, Alpha-lactalbumin. Lactose synthase creates lactose through bonding galactose from UDP to glucose through a glycosidic bond. Although GT is found in many tissues in the body, Alpha-lactalbumin is only found on the inner surface of the Golgi in the mammary glands, limiting lactose production to the mammaries.
References
Lactose Synthesis References
Lei KJ, Shelly LL, Pan CJ, Sidbury JB, Chou JY: Mutations in the glucose-6-phosphatase gene that cause glycogen storage disease type 1a. Science. 1993 Oct 22;262(5133):580-3. doi: 10.1126/science.8211187.
Pubmed: 8211187
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. doi: 10.1038/nature04689.
Pubmed: 16625196
Peng HL, Chang HY: Cloning of a human liver UDP-glucose pyrophosphorylase cDNA by complementation of the bacterial galU mutation. FEBS Lett. 1993 Aug 23;329(1-2):153-8. doi: 10.1016/0014-5793(93)80213-e.
Pubmed: 8354390
Duggleby RG, Chao YC, Huang JG, Peng HL, Chang HY: Sequence differences between human muscle and liver cDNAs for UDPglucose pyrophosphorylase and kinetic properties of the recombinant enzymes expressed in Escherichia coli. Eur J Biochem. 1996 Jan 15;235(1-2):173-9. doi: 10.1111/j.1432-1033.1996.00173.x.
Pubmed: 8631325
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Stahl JA, Leone A, Rosengard AM, Porter L, King CR, Steeg PS: Identification of a second human nm23 gene, nm23-H2. Cancer Res. 1991 Jan 1;51(1):445-9.
Pubmed: 1988104
Gilles AM, Presecan E, Vonica A, Lascu I: Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. J Biol Chem. 1991 May 15;266(14):8784-9.
Pubmed: 1851158
Postel EH, Berberich SJ, Flint SJ, Ferrone CA: Human c-myc transcription factor PuF identified as nm23-H2 nucleoside diphosphate kinase, a candidate suppressor of tumor metastasis. Science. 1993 Jul 23;261(5120):478-80. doi: 10.1126/science.8392752.
Pubmed: 8392752
Van Rompay AR, Johansson M, Karlsson A: Phosphorylation of deoxycytidine analog monophosphates by UMP-CMP kinase: molecular characterization of the human enzyme. Mol Pharmacol. 1999 Sep;56(3):562-9. doi: 10.1124/mol.56.3.562.
Pubmed: 10462544
Pearman AT, Castro-Faria-Neto HC, McIntyre TM, Prescott SM, Stafforini DM: Characterization of human UMP-CMP kinase enzymatic activity and 5' untranslated region. Life Sci. 2001 Oct 5;69(20):2361-70. doi: 10.1016/s0024-3205(01)01322-4.
Pubmed: 11681623
Liou JY, Dutschman GE, Lam W, Jiang Z, Cheng YC: Characterization of human UMP/CMP kinase and its phosphorylation of D- and L-form deoxycytidine analogue monophosphates. Cancer Res. 2002 Mar 15;62(6):1624-31.
Pubmed: 11912132
Tyfield L, Reichardt J, Fridovich-Keil J, Croke DT, Elsas LJ 2nd, Strobl W, Kozak L, Coskun T, Novelli G, Okano Y, Zekanowski C, Shin Y, Boleda MD: Classical galactosemia and mutations at the galactose-1-phosphate uridyl transferase (GALT) gene. Hum Mutat. 1999;13(6):417-30. doi: 10.1002/(SICI)1098-1004(1999)13:6<417::AID-HUMU1>3.0.CO;2-0.
Pubmed: 10408771
Lin HC, Kirby LT, Ng WG, Reichardt JK: On the molecular nature of the Duarte variant of galactose-1-phosphate uridyl transferase (GALT). Hum Genet. 1994 Feb;93(2):167-9. doi: 10.1007/bf00210604.
Pubmed: 8112740
Reichardt JK, Berg P: Cloning and characterization of a cDNA encoding human galactose-1-phosphate uridyl transferase. Mol Biol Med. 1988 Apr;5(2):107-22.
Pubmed: 2840550
Rungaldier S, Oberwagner W, Salzer U, Csaszar E, Prohaska R: Stomatin interacts with GLUT1/SLC2A1, band 3/SLC4A1, and aquaporin-1 in human erythrocyte membrane domains. Biochim Biophys Acta. 2013 Mar;1828(3):956-66. doi: 10.1016/j.bbamem.2012.11.030. Epub 2012 Dec 3.
Pubmed: 23219802
Mueckler M, Caruso C, Baldwin SA, Panico M, Blench I, Morris HR, Allard WJ, Lienhard GE, Lodish HF: Sequence and structure of a human glucose transporter. Science. 1985 Sep 6;229(4717):941-5. doi: 10.1126/science.3839598.
Pubmed: 3839598
Hall L, Craig RK, Edbrooke MR, Campbell PN: Comparison of the nucleotide sequence of cloned human and guinea-pig pre-alpha-lactalbumin cDNA with that of chick pre-lysozyme cDNA suggests evolution from a common ancestral gene. Nucleic Acids Res. 1982 Jun 11;10(11):3503-15. doi: 10.1093/nar/10.11.3503.
Pubmed: 6285305
Hall L, Emery DC, Davies MS, Parker D, Craig RK: Organization and sequence of the human alpha-lactalbumin gene. Biochem J. 1987 Mar 15;242(3):735-42. doi: 10.1042/bj2420735.
Pubmed: 2954544
Masri KA, Appert HE, Fukuda MN: Identification of the full-length coding sequence for human galactosyltransferase (beta-N-acetylglucosaminide: beta 1,4-galactosyltransferase). Biochem Biophys Res Commun. 1988 Dec 15;157(2):657-63. doi: 10.1016/s0006-291x(88)80300-0.
Pubmed: 3144273
Watzele G, Berger EG: Near identity of HeLa cell galactosyltransferase with the human placental enzyme. Nucleic Acids Res. 1990 Dec 11;18(23):7174. doi: 10.1093/nar/18.23.7174.
Pubmed: 2124683
Mengle-Gaw L, McCoy-Haman MF, Tiemeier DC: Genomic structure and expression of human beta-1,4-galactosyltransferase. Biochem Biophys Res Commun. 1991 May 15;176(3):1269-76. doi: 10.1016/0006-291x(91)90423-5.
Pubmed: 1903938
Nizon M, Huber C, De Leonardis F, Merrina R, Forlino A, Fradin M, Tuysuz B, Abu-Libdeh BY, Alanay Y, Albrecht B, Al-Gazali L, Basaran SY, Clayton-Smith J, Desir J, Gill H, Greally MT, Koparir E, van Maarle MC, MacKay S, Mortier G, Morton J, Sillence D, Vilain C, Young I, Zerres K, Le Merrer M, Munnich A, Le Goff C, Rossi A, Cormier-Daire V: Further delineation of CANT1 phenotypic spectrum and demonstration of its role in proteoglycan synthesis. Hum Mutat. 2012 Aug;33(8):1261-6. doi: 10.1002/humu.22104. Epub 2012 May 22.
Pubmed: 22539336
Balasubramanian K, Li B, Krakow D, Nevarez L, Ho PJ, Ainsworth JA, Nickerson DA, Bamshad MJ, Immken L, Lachman RS, Cohn DH: MED resulting from recessively inherited mutations in the gene encoding calcium-activated nucleotidase CANT1. Am J Med Genet A. 2017 Sep;173(9):2415-2421. doi: 10.1002/ajmg.a.38349. Epub 2017 Jul 25.
Pubmed: 28742282
Laccone F, Schoner K, Krabichler B, Kluge B, Schwerdtfeger R, Schulze B, Zschocke J, Rehder H: Desbuquois dysplasia type I and fetal hydrops due to novel mutations in the CANT1 gene. Eur J Hum Genet. 2011 Nov;19(11):1133-7. doi: 10.1038/ejhg.2011.101. Epub 2011 Jun 8.
Pubmed: 21654728
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